What is the best next step for a patient with impaired renal function (serum creatinine 2.1, GFR 34) and a history of gastric reflux disease, who is currently taking pantoprazole (proton pump inhibitor), and has leukocytosis (12,000 WBC)?

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Management of Acute Kidney Injury in a Patient with Elevated Creatinine

The best next step in this patient with acute kidney injury is to discontinue pantoprazole due to suspected proton pump inhibitor-induced acute tubulointerstitial nephritis. 1, 2, 3

Assessment of Current Renal Function

This 58-year-old man presents with:

  • Elevated serum creatinine of 2.1 mg/dL (increased from baseline of 0.9 mg/dL)
  • Reduced GFR of 34 mL/min
  • Pyuria (10 WBC per field)
  • Hematuria (5 RBC per field)
  • Leukocytosis (12,000 WBC with 61% neutrophils)
  • Low-grade fever (99.8°F)

These findings are consistent with acute kidney injury (AKI), specifically meeting RIFLE criteria for "Injury" with a >2-fold increase in serum creatinine from baseline 4.

Identifying the Cause of AKI

The patient is currently taking pantoprazole for gastric reflux disease. Proton pump inhibitors (PPIs) like pantoprazole are known to cause acute tubulointerstitial nephritis (AIN), which presents with:

  • Elevated creatinine
  • Pyuria
  • Fever
  • Leukocytosis
  • Recent exposure to the causative medication (typically within weeks to months)

According to the FDA drug label, acute tubulointerstitial nephritis has been observed in patients taking PPIs and may occur at any point during PPI therapy 1. Multiple case reports have documented pantoprazole-induced AIN 2, 3, 5.

Management Algorithm

  1. Discontinue the offending agent (pantoprazole) - This is the critical first step in management

    • The FDA label specifically states: "Discontinue pantoprazole sodium and evaluate patients with suspected acute TIN" 1
  2. Evaluate for alternative causes of AKI:

    • Pre-renal: Recent volume depletion, hypotension
    • Intrinsic: Other nephrotoxic medications, contrast exposure
    • Post-renal: Obstruction
  3. Monitor renal function:

    • Check serum creatinine every 2-3 days until improvement
    • Monitor electrolytes, especially potassium
  4. Consider corticosteroid therapy if no improvement within 3-5 days after drug discontinuation

    • Prednisone 0.5-1 mg/kg/day has been used successfully in case reports 2, 5
  5. Provide supportive care:

    • Maintain adequate hydration
    • Consider one liter of intravenous fluids if evidence of volume depletion
    • Avoid other nephrotoxic agents

Rationale for Discontinuing Pantoprazole

  1. Temporal relationship: The rise in creatinine from 0.9 to 2.1 mg/dL suggests AKI developing during the patient's hospitalization, with pantoprazole being a likely contributor.

  2. Clinical presentation: The combination of fever, pyuria, hematuria, and leukocytosis is consistent with drug-induced AIN.

  3. Established causality: Multiple case reports have documented pantoprazole as a cause of AIN 2, 3, 5.

  4. Guideline recommendation: The FDA label explicitly recommends discontinuation of pantoprazole when AIN is suspected 1.

  5. Reversibility: PPI-induced AIN is typically reversible with early discontinuation of the offending agent 2, 5.

Why Other Options Are Not Preferred

  • Starting temporary antibiotics: While the patient has leukocytosis, there are no clear signs of infection requiring antibiotics. Treating with antibiotics without a clear source would add another potential nephrotoxin.

  • Ordering ultrasonography: While imaging may be helpful to rule out obstruction, the clinical picture strongly suggests drug-induced AIN, and discontinuation of the offending agent should not be delayed.

  • Giving IV fluids: While hydration is important in AKI management, addressing the underlying cause (drug-induced AIN) by discontinuing pantoprazole is the priority. Excessive fluid administration without addressing the primary cause could potentially worsen the patient's condition.

Important Considerations

  • If renal function does not improve after discontinuation of pantoprazole, consider nephrology consultation and possible kidney biopsy.

  • The KDIGO guidelines recommend monitoring serum creatinine prior to each dose of potentially nephrotoxic medications 4.

  • PPI-induced AIN can occur at any time during treatment, even after months or years of use 1.

  • Recovery of renal function may take days to weeks after discontinuation of the offending agent.

References

Research

Acute interstitial nephritis due to pantoprazole.

The Annals of pharmacotherapy, 2004

Research

Pantoprazole-induced acute interstitial nephritis.

Journal of nephrology, 2004

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pantoprazole-induced acute kidney injury: A case report.

Experimental and therapeutic medicine, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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